Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination

Jennifer K. Ness, Amanda A. Skiles, Eng Hui Yap, Jorge E. Fajardo, Andras Fiser, Nikos Tapinos

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination.

Original languageEnglish (US)
JournalGLIA
DOIs
StateAccepted/In press - 2016

Fingerprint

Epigenetic Repression
Methyltransferases
Schwann Cells
Genes
Chromatin
Neuregulins
Nucleotide Motifs
RNA Polymerase II
Histones
Phenotype

Keywords

  • Chromatin
  • PNS myelination
  • Transcriptional repression

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination. / Ness, Jennifer K.; Skiles, Amanda A.; Yap, Eng Hui; Fajardo, Jorge E.; Fiser, Andras; Tapinos, Nikos.

In: GLIA, 2016.

Research output: Contribution to journalArticle

@article{cd44e787fe744914914f6a3fc81f6285,
title = "Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination",
abstract = "Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination.",
keywords = "Chromatin, PNS myelination, Transcriptional repression",
author = "Ness, {Jennifer K.} and Skiles, {Amanda A.} and Yap, {Eng Hui} and Fajardo, {Jorge E.} and Andras Fiser and Nikos Tapinos",
year = "2016",
doi = "10.1002/glia.22977",
language = "English (US)",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination

AU - Ness, Jennifer K.

AU - Skiles, Amanda A.

AU - Yap, Eng Hui

AU - Fajardo, Jorge E.

AU - Fiser, Andras

AU - Tapinos, Nikos

PY - 2016

Y1 - 2016

N2 - Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination.

AB - Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination.

KW - Chromatin

KW - PNS myelination

KW - Transcriptional repression

UR - http://www.scopus.com/inward/record.url?scp=84961719979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961719979&partnerID=8YFLogxK

U2 - 10.1002/glia.22977

DO - 10.1002/glia.22977

M3 - Article

C2 - 27017927

AN - SCOPUS:84961719979

JO - GLIA

JF - GLIA

SN - 0894-1491

ER -